Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition.
EMBO J
; 29(22): 3787-96, 2010 Nov 17.
Article
em En
| MEDLINE
| ID: mdl-20959806
ABSTRACT
Protein O-phosphorylation often occurs reciprocally with O-GlcNAc modification and represents a regulatory principle for proteins. O-phosphorylation of serine by glycogen synthase kinase-3ß on Snail1, a transcriptional repressor of E-cadherin and a key regulator of the epithelial-mesenchymal transition (EMT) programme, results in its proteasomal degradation. We show that by suppressing O-phosphorylation-mediated degradation, O-GlcNAc at serine112 stabilizes Snail1 and thus increases its repressor function, which in turn attenuates E-cadherin mRNA expression. Hyperglycaemic condition enhances O-GlcNAc modification and initiates EMT by transcriptional suppression of E-cadherin through Snail1. Thus, dynamic reciprocal O-phosphorylation and O-GlcNAc modification of Snail1 constitute a molecular link between cellular glucose metabolism and the control of EMT.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Acetilglucosamina
/
Fatores de Transcrição
/
Hiperglicemia
Limite:
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2010
Tipo de documento:
Article